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PubMed2001

Purine metabolism during white spruce somatic embryo development: salvage of adenine, adenosine, and inosine.

Contribution of the adenine, adenosine and inosine salvage to the purine nucleotide and nucleic acid biosynthesis during white spruce (Picea glauca) somatic embryo maturation was estimated by in situ assays using [8-(14)C]adenine, [8-(14)C]adenosine and [8-(14)C]inosine. The salvage of adenine and adenosine was high during the initial stages of embryo maturation, characterized by rapid cell proliferation, but it declined upon further embryo development. Inosine salvage activity was always much lower than that observed for adenine and adenosine. Consistent with these results, activities of adenine phosphoribosyltransferase (APRT) and adenosine kinase (AK) measured in the embryo extracts in vitro were much higher than the activity of inosine kinase (IK) during all stages of embryo development. Utilization of adenosine and inosine for nucleotide and nucleic acid synthesis was found to be regulated by the enzymes AK and IK, as the pattern of their activities was very similar to the activity of adenosine and inosine salvage, estimated with exogenously supplied precursors. However, little correlation between salvage of adenine and activity of APRT was found throughout somatic embryo maturation. As no adenosine nucleosidase activity was found in white spruce embryos, adenosine, but not adenine, seems to be the major end product of adenylate catabolism and becomes the predominant substrate for purine salvage in vivo. Thus, adenosine salvage appeared to have the most important role in white spruce embryos. Studies on the metabolic fate of [8-(14)C]adenine and [8-(14)C]adenosine suggest that turnover of adenine nucleotides is rapid, as some of them are utilized for nucleic acid synthesis. In contrast, most of [8-(14)C]inosine taken up by the embryos seems to be directly catabolized by the conventional purine catabolic pathway via ureides in all stages of embryo maturation.

Journal Article↗
PubMed1997

A novel process of inosine 5'-monophosphate production using overexpressed guanosine/inosine kinase.

A novel process for producing inosine 5'-monophosphate (5'-IMP) has been demonstrated. The process consists of two sequential bioreactions; the first is a fermentation of inosine by a mutant of Corynebacterium ammoniagenes, and the second is a unique phosphorylating reaction of inosine by guanosine/inosine kinase (GIKase). GIKase was produced by an Escherichia coli recombinant strain, MC1000(pIK75), which overexpressed the enzyme up to 50% of the total cellular protein. The overproducing plasmid, pIK75, which was randomly screened out from deletion plasmids with various lengths of intermediate sequence between the E. coli trpL Shine-Dalgarno sequence, derived from the vector plasmid, and the start codon of the GIKase structural gene. In pIK75, the start ATG was placed 16 bp downstream of the trpL Shine-Dalgarno sequence under the control of the E. coli trp promoter. Fermentation of inosine and its phosphorylation were sequentially performed in a 5-1 jar fermenter. At the end of inosine fermentation by C. ammoniagenes KY13761, culture broth of MC1000(pIK75) was mixed with that of KY13761 to start the phosphorylating reaction. Inosine in the reaction mixture was stoichiometrically phosphorylated, and 91 mM 5'-IMP accumulated in a 12-h reaction. This new biological process has advantages over traditional methods for producing 5'-IMP.

Base Sequence↗
PubMed1998

Adenosine, inosine, and guanosine protect glial cells during glucose deprivation and mitochondrial inhibition: correlation between protection and ATP preservation.

The purpose of this study was to determine the mechanism by which adenosine, inosine, and guanosine delay cell death in glial cells (ROC-1) that are subjected to glucose deprivation and mitochondrial respiratory chain inhibition with amobarbital (GDMI). ROC-1 cells are hybrid cells formed by fusion of a rat oligodendrocyte and a rat C6 glioma cell. Under GDMI, ATP was depleted rapidly from ROC-1 cells, followed on a much larger time scale by a loss of cell viability. Restoration of ATP synthesis during this interlude between ATP depletion and cell death prevented further loss of viability. Moreover, the addition of adenosine, inosine, or guanosine immediately before the amobarbital retarded the decline in ATP and preserved cell viability. The protective effects on ATP and viability were dependent on nucleoside concentration between 50 and 1,500 microM. Furthermore, protection required nucleoside transport into the cell and the continued presence of nucleoside during GDMI. A significant positive correlation between ATP content at 16 min and cell viability at 350 min after the onset of GDMI was established (r = 0.98). Modest increases in cellular lactate levels were observed during GDMI (1.2 nmol/mg/min lactate produced); however, incubation with 1,500 microM inosine or guanosine increased lactate accumulation sixfold. The protective effects of inosine and guanosine on cell viability and ATP were >90% blocked after treatment with 50 microM BCX-34, a nucleoside phosphorylase inhibitor. Accordingly, lactate levels also were lower in BCX-34-treated cells incubated with inosine or guanosine. We conclude that under GDMI, the ribose moiety of inosine and guanosine is converted to phosphorylated glycolytic intermediates via the pentose phosphate pathway, and its subsequent catabolism in glycolysis provides the ATP necessary for maintaining plasmalemmal integrity.

Adenine Nucleotides↗
PubMed1990

The efficacy of inosine pranobex in preventing the acquired immunodeficiency syndrome in patients with human immunodeficiency virus infection. The Scandinavian Isoprinosine Study Group.

We performed a randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of inosine pranobex (Isoprinosine) [corrected] in the treatment of patients with human immunodeficiency virus (HIV) infection but without manifest acquired immunodeficiency syndrome (AIDS). A total of 866 patients were enrolled in 21 centers in Denmark and Sweden. The patients were stratified in three groups according to their CD4+ cell count and randomly assigned to receive either inosine pranobex (1 g three times a day) (n = 429) or matching placebo (n = 437) for 24 weeks. Of the 831 patients who could be evaluated, AIDS developed in 17 in the placebo group as compared with 2 in the inosine pranobex group (P less than 0.001; odds ratio, 8.6 [95 percent confidence limits, 2.2 and 52.6]). There were no significant differences between the groups with respect to changes in CD4+ cell count or the development of other HIV-related conditions, with the exception of thrush, which developed in fewer patients in the inosine pranobex group (P = 0.05). No serious side effects were observed. We conclude that treatment with inosine pranobex delays progression to AIDS in patients with HIV infection. The duration of this beneficial effect, the optimal dose, and the mode of action of inosine pranobex remain to be clarified.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Leishmania donovani: pilot study for evaluation of therapeutic effects of inosine analogs against amastigotes in vitro and in vivo.

The inhibition of carbocyclic inosine (C-Ino), 3'-deoxyinosine (3'-dI), and 3'-fluoroinosine (3'-FI) to Leishmania donovani amastigotes was examined. J774.1 cells (a mouse macrophage line) were cultured in GIT medium with lipopolysaccharide and hemin and infected with the parasite. C-Ino (3 microM) completely inhibited and 3'-dI (30 microM) reduced to 40% the infection rate on Day 6 after infection. Pentostam (30 microM) resulted in a 38% infection rate. The therapeutic efficacies of nonentrapped free and liposome-entrapped inosine analogs were tested in mice infected with L. donovani. The mice were injected intravenously five times on alternate days, beginning 2 days after infection. Treatment with the nonentrapped free inosine analog of C-Ino (100 mg/kg), 3'-dI (100 mg/kg), or 3'-FI (50 mg/kg) resulted in an LDU that was 94, 68, or 73% lower, respectively, than the control values. Treatment with the corresponding entrapped inosine analog (10 mg/kg) caused decreases of 90, 69, or 68% LDU, respectively. The entrapped inosine analogs were inhibitory at doses one-fifth to one-tenth of the nonentrapped free inosine analogs. C-Ino had the strongest inhibitory effect among the three analogs tested in vitro and in vivo. Liposome-entrapped C-Ino had no severe side effects, although spleen weight increased. The agent may be useful as an anti-leishmanial drug.

Animals↗
PubMed2002

Inosine modulates gut barrier dysfunction and end organ damage in a model of ischemia-reperfusion injury.

INTRODUCTION: Gut barrier failure is an important source of morbidity in critically ill patients, and patients undergoing aortic cross-clamp. Inosine, an endogenous purine nucleoside without known side effects, formed from the breakdown of adenosine by adenosine deaminase, has been shown to modify the effects of hypoxia on various tissues, including the heart and the brain. MATERIALS AND METHODS: This study examined the effect of inosine on ischemia-reperfusion-induced gut barrier dysfunction and on the associated lung injury. Twenty-four male Sprague-Dawley rats were divided into three groups. Eight were subjected to 60 min of superior mesenteric artery occlusion followed by 4 h of reperfusion. Eight had 100 mg/kg inosine prior to ischemia-reperfusion and 8 had sham laparotomy with encircling but not occlusion of the superior mesenteric artery. RESULTS: Rats treated with inosine had significantly less gut barrier dysfunction. Rats subjected to SMAO sustained a substantial lung injury and this was attenuated by inosine treatment. Serum cytokine levels were also significantly lower. CONCLUSIONS: We conclude that inosine has a beneficial effect in modulating both gut barrier dysfunction and distant organ injury in response to gut ischemia-reperfusion.

Animals↗
PubMed1985

Synergistic interaction in Jensen tumor cells of two modes of exposure to inosine that potentiate the cytotoxicity of 5-fluorouracil.

The cytotoxicity resulting from a 1-h exposure of Jensen tumor (JT) cells to 5-fluorouracil (FUra), quantified in terms of growth delay, was potentiated 4.1-fold if inosine was included in the culture medium for 30 min prior to and for 1 h concurrently with drug uptake. In contrast, as reported previously, protection from FUra toxicity is induced if the cells are exposed successively to inosine for 1.5 h and to FUra for 1 h. Anabolic conversion of radiolabeled FUra to free and polymeric nucleotides was stimulated by the cytotoxicity-enhancing mode of inosine exposure but inhibited by the inosine exposure that protects against FUra. Continuous exposure of JT cells to inosine after a 1-h uptake of FUra was reported earlier to potentiate drug efficacy 5-fold. Treatment of cultures by both modes of inosine exposure that enhance FUra cytotoxicity resulted in a 15.8-fold potentiation of the latter.

Animals↗
PubMed2005

Extracellular inosine modulates ERK 1/2 and p38 phosphorylation in cultured Sertoli cells: possible participation in TNF-alpha modulation of ERK 1/2.

Extracellular ATP and adenosine modulation of MAPKs is well described in different cells types, but few studies have addressed the effects of extracellular inosine on these kinases. Previous results showed that hydrogen peroxide and TNF-alpha increase extracellular inosine concentration in cultured Sertoli cells and this nucleoside protects Sertoli cells against hydrogen peroxide induced damage and participates in TNF-alpha induced nitric oxide production. In view of the fact that MAPKs are key mediators of the cellular response to a large variety of stimuli, we investigated the effect of extracellular inosine on the phosphorylation of ERK 1/2 and p38 MAPKs in cultured Sertoli cells. The involvement of this nucleoside in the activation of ERK 1/2 by TNF-alpha was also investigated. Inosine and the selective A1 adenosine receptor agonist R-PIA increases the phosphorylation of ERK 1/2 and p38, and this was blocked by the selective A1 adenosine receptors antagonists, CPT and DPCPX. These antagonists also inhibited TNF-alpha increase in the phosphorylation of ERK 1/2. TNF-alpha also rapidly augmented extracellular inosine concentration in cultured Sertoli cells. These results show that extracellular inosine modulates ERK 1/2 and p38 in cultured Sertoli cells, possible trough A1 adenosine receptor activation. This nucleoside also participates in TNF-alpha modulation of ERK 1/2.

Animals↗
PubMed2004

Inosine reverses the inhibitory effects of the L-type Ca2+ channel antagonist, DM-BODIPY-dihydropyridine, on neuritogenesis in an in vitro rat superior cervical ganglia axotomy model.

It has recently been demonstrated that L-type calcium channel antagonism with the fluorescent dihydropyridine DM-BODIPY-dihydropyridine (DMBD) inhibits neurite regeneration in rat superior cervical ganglia (SCG). The neuritogenic effects of inosine have been described in various models and the mechanism is thought to be N-kinase dependent. Because of the final common pathway between calcium dependent and N-kinase dependent neurite regeneration it was hypothesized that inosine would increase regeneration in normally regenerating SCG and reverse the inhibitory effects of DMBD on regenerating SCG. An in vitro model of rat SCG injury, where mature neurites are transected and observed at 2 and 24 h, was used to assess the effects of inosine on DMBD treated neurons. Results demonstrate a significant inhibition of growth in DMBD treated cultures, significantly increased growth in the inosine + DMBD treated SCG over DMBD treated cells and significantly increased growth in the inosine alone treated group over control cells. There is also evidence that inosine + DMBD treatment promotes linear growth of neurites. The implications of the findings are discussed.

Animals↗
PubMed1999

Inosine and guanosine preserve neuronal and glial cell viability in mouse spinal cord cultures during chemical hypoxia.

Murine spinal cord primary mixed cultures were treated with the respiratory inhibitor, rotenone, to mimic hypoxic conditions. Under these conditions neurons rapidly underwent oncosis (necrosis) with a complete loss in viability occurring within 260 min; however, astrocytes, which accounted for most of the cell population, died more slowly with 50% viability occurring at 565 min. Inosine preserved both total cell and neuronal viability in a concentration-dependent manner. The time of inosine addition relative to hypoxic insult was critical with the most effective protection occurring when inosine was added just prior to or within 5 min after insult. Inosine was ineffective when added 30 min after hypoxic insult. The effect of guanosine was similar to that of inosine. Treatment of cultures with BCX-34, a purine nucleoside phosphorylase inhibitor, prevented protection by inosine or guanosine, suggesting involvement of a purine nucleoside phosphorylase in the nucleoside protective effect.

Anaerobiosis↗
PubMed1999

Enhanced accumulation of pericardial fluid adenosine and inosine in patients with coronary artery disease.

Adenosine and inosine are believed to have cardioprotective effects. However, little is known about their possible role in the metabolic autoregulation of human coronaries and in pathologic conditions with supply/demand imbalance of the heart such as coronary artery disease. Since these low molecular weight nucleosides freely diffuse through the monolayer of the visceral pericardium, adenosine and inosine concentrations in pericardial fluid may well reflect the conditions in cardiac interstitium. The pericardial fluid and systemic venous blood adenosine and inosine concentrations were measured in 98 human subjects undergoing heart surgery for coronary artery disease or valvular heart disease. Adenosine and inosine concentrations were measured by HPLC with UV detection. In subjects with coronary artery disease pericardial fluid nucleoside concentrations were significantly higher than in patients with valvular heart disease (adenosine: 1545 (996-3146) nmol/L [median (25th-75th quartiles)] vs. 738 (390-2527) nmol/L, P<0.01; inosine: 658 (321-1331) nmol/L vs. 347 (159-1037) nmol/L, P<0.05), while in both patient groups pericardial fluid nucleoside concentrations were higher by an order of magnitude than in venous plasma. Our results show the enhanced release of adenosine and inosine by the ischemic myocardium as a marker of supply/demand imbalance and support the hypothesis that these cardiac nucleosides may have an important role in the adaptation of coronary blood flow in human coronary artery disease.

Adenosine↗
PubMed2005

Secondary degeneration reduced by inosine after spinal cord injury in rats.

STUDY DESIGN: Assessment of the potential protective effects of inosine on an animal model of spinal cord injury. OBJECTIVES: Our previous studies have demonstrated that inosine can directly protect neurons in vitro from zinc-induced injury and axotomized retinal ganglion cells of rats in vivo. This investigation was carried out to examine the possible protective effects of inosine on spinal cord secondary degeneration. SETTING: Institute of Neurosciences, The Fourth Military Medical University, Xi'an, China. METHODS: Compressive spinal cord injury (95-g load for 1 min) model was established in rats, and inosine was administrated beginning at different time points (2, 12, or 24 h) after spinal cord injury. RESULTS: Using terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) technique and hematoxylin and eosin staining, our study demonstrated that administration of inosine as late as 12 h after injury significantly reduced the total volume of spinal cord degenerative areas and the number of apoptotic cells 3 days following the trauma. CONCLUSION: Inosine can significantly reduce the spread of secondary degeneration and the cell death following spinal cord injury in adult rats. These findings may find a clinical application in the treatment of acute spinal cord injury.

Animals↗
PubMed2000

Cloning of a novel inosine-guanosine transporter gene from Leishmania donovani by functional rescue of a transport-deficient mutant.

Purine transport is an indispensable nutritional function for protozoan parasites, since they are incapable of purine biosynthesis and must, therefore, acquire purines from the host milieu. Exploiting a mutant cell line (FBD5) of Leishmania donovani deficient in inosine and guanosine transport activity, the gene encoding this transporter (LdNT2) has been cloned by functional rescue of the mutant phenotype. LdNT2 encodes a polypeptide of 499 amino acids that shows substantial homology to other members of the equilibrative nucleoside transporter family. Molecular analysis revealed that LdNT2 is present as a single gene copy within the leishmanial genome and encodes a single transcript of 3 kilobase pairs. Transfection of FBD5 parasites with LdNT2 re-established their ability to take up inosine and guanosine with a concurrent restoration of sensitivity to the inosine analog formycin B. Kinetic analyses reveal that LdNT2 is highly specific for inosine (K(m) = 0.3 micrometer) and guanosine (K(m) = 1.7 micrometer) and does not recognize other naturally occurring nucleosides. Expression of LdNT2 cRNA in Xenopus oocytes significantly augmented their ability to take up inosine and guanosine, establishing that LdNT2 by itself suffices to mediate nucleoside transport. These results authenticate genetically and biochemically that LdNT2 is a novel nucleoside transporter with an unusual and strict specificity for inosine and guanosine.

Amino Acid Sequence↗
PubMed1983

Inosine infusion in dogs with acute ischaemic left ventricular failure: favourable effects on myocardial performance and metabolism.

Haemodynamic and metabolic effects of inosine were examined during acute left ventricular (LV) failure in closed-chest anaesthetised dogs. Embolisation of the left main coronary artery with 50 microm plastic microspheres induced severe depression of LV function, and the dogs remained in stable failure throughout the experimental period as shown in the untreated control dogs (n = 4). Intravenous infusion of inosine 3.8 to 7.5 mg . min-1 . kg-1 caused an increase in maximum LVdP/dt from 290 +/- 32 (mean +/- SEM, n = 8) to 376 +/- 39 kPa . s-1 and a decrease in LV end-diastolic pressure from 3.6 +/- 0.2 to 2.5 +/- 0.1 kPa. Total peripheral resistance decreased from 10.2 +/- 1.0 to 7.4 +/- 0.7 kPa . litre-1 min, and cardiac output increased from 1.64 +/- 0.17 to 2.27 +/- 0.23 litre . min-1 during inosine infusion. Myocardial blood flow increased from 65 +/- 10 to 94 +/- 16 cm3 . min-1 . 100 g-1 with no change in myocardial oxygen consumption. Inosine markedly decreased arterial concentrations and myocardial uptake of FFA. Arterial concentrations of glucose were moderately decreased while myocardial uptake of glucose showed a non-significant increase. Inosine markedly increased myocardial uptake of lactate. These metabolic changes were associated with increased plasma concentrations of insulin. In conclusion, inosine improved myocardial performance and increased myocardial uptake of carbohydrates relative to FFA during acute ischaemic LV failure in dogs.

Animals↗
PubMed1989

Apparent inosine uptake by the human heart.

Although inosine has been used clinically to support the myocardium, no data are available on the fate of exogenous inosine in the human heart. We therefore infused six patients, catheterised for coronary angiography, with inosine (5 mg.kg-1.min-1 intravenously) for 6 minutes. Before infusion, the arterio-venous difference of inosine, hypoxanthine and xanthine across the heart was nil. During infusion, arterial inosine increased substantially, exceeding the coronary sinus concentration by a maximum of 200 (SEM 53) mumol.litre-1, p = 0.02, at the fourth minute. Arterial hypoxanthine and xanthine also increased, while the arterio-venous difference became 16(11) and 10(3) (p = 0.04) mumol.litre-1, respectively. Left ventricular dP/dtmax increased by 22(7)% (p = 0.04) at the end of infusion. Thus, there seemed to be substantial uptake of inosine by the human heart, followed by improvement in haemodynamics.

Adult↗
PubMed1991

Synthesis of RNA containing inosine: analysis of the sequence requirements for the 5' splice site of the Tetrahymena group I intron.

Two protected derivatives of the ribonucleoside inosine have been prepared to serve as building blocks for phosphoramidite-based synthesis of RNA. Two different synthetic routes address the unusual solubility characteristics of inosine and its derivatives. The final products of the different synthetic pathways, 5'-O-(dimethoxytrityl)-2'-O-(t-butyldimethylsiyl) inosine 3'-O-(beta-cyanoethyldiisopropylamino) phosphoramidite 5a, and O6-p-nitrophenylethyl-5'-O-(dimethoxytrityl)-2'-O-(t-butyldimethylsilyl) inosine 3'-O-(methyldiisopropylamino) phosphoramidite 5b, were chemically incorporated into short oligoribonucleotides which also contained the four standard ribonucleoside bases. The oligomers were chosen to study base-specific interactions between an RNA substrate and an RNA enzyme derived from the Group I Tetrahymena self-splicing intron. The oligomers were shown to be biochemically competent using a trans cleavage assay with the modified Tetrahymena intron. The results confirm the dependence of the catalytic activity on a wobble base pair, rather than a Watson-Crick base pair, in the helix at the 5'-splice site. Furthermore, comparison of guanosine and inosine in a wobble base pair allows one to assess the importance of the guanine 2-amino group for biological activity. The preparation of the inosine phosphoramidites adds to the repertoire of base analogues available for the study of RNA catalysis and RNA-protein interactions.

Animals↗
PubMedDate not supplied

Relaxation of the isolated coronary artery by inosine: noninvolvement of the adenosine receptor.

The relaxation responses to adenosine and its analog inosine were compared in isolated canine coronary arterial rings (1-2 mm o.d.). The rings were contracted with prostaglandin F2 alpha (PGF2 alpha) and relaxed by progressively increasing the nucleoside concentration in the bathing medium. The maximal relaxation (Rmax) was expressed as a percentage of the increase in isometric tension caused by PGF2 alpha. All 15 rings responded to inosine, but only 10 responded to adenosine. In the 10 rings responding to both nucleosides, the ED50 (geometric mean with 95% confidence limits) for adenosine and inosine was 0.89 (0.76-1.26) and 224 (166-302) microM, respectively (p less than 0.001). However, in these 10 rings, the Rmax for adenosine was much less than that for inosine (p less than 0.05); thus, the mean ratio of adenosine Rmax/inosine Rmax was only 0.56 +/- 0.15 (SE). In further experiments, the methylxanthine aminophylline completely abolished the relaxation response to adenosine but did not affect the response to inosine. These results suggested that inosine relaxes the coronary artery by stimulation of a site distinct from the vascular adenosine receptor.

Adenosine↗
PubMed1991

Effect of inosine on function and adenine nucleotide content of the isolated working rat heart: studies of postischemic reperfusion.

Inosine added to the perfusion medium for isolated working rat heart induced a dose-dependent coronary vasodilator and positive functional effect. Inosine increased coronary flow (ml/min) from 11.8 +/- 0.5 (control, n = 16) to 15.6 +/- 0.6 (0.1 mM, n = 10), to 18.2 +/- 1.1 (0.5 mM, n = 6), and to 18.4 +/- 0.8 (1.0 mM, n = 14). Left ventricular systolic pressure was increased (LVSP, mm Hg) from 72.5 +/- 1.1 (control) to 75.4 +/- 1.7 (0.1 mM) to 78.7 +/- 2.1 (0.5 mM) and to 82.6 +/- 1.5 (1.0 mM). and cardiac output (CO, ml/min) from 26.4 +/- 2.0 (control) to 29.6 +/- 2.3 (0.1 mM), to 30.2 +/- 3.5 (0.5 mM), and to 37.4 +/- 2.0 (1.0 mM). At the end of 30-min reperfusion after a 15-min period of global total ischemia (n = 9), the functional parameters were significantly reduced (coronary flow 8.5 +/- 0.4 ml/min, LVSP 63 +/- 1.9 mm Hg, CO 13.6 +/- 1.9 ml/min). When inosine was present in the perfusion medium during the entire experimental protocol, coronary flow and heart function were also enhanced in a dose-dependent manner. The content of cardiac ATP (mumol/g) was decreased at the end of the 15-min ischemic period (1.89 +/- 0.17, n = 7; control 3.85 +/- 0.05, n = 4), and inosine had no effect. At the end of the 30-min postischemic reperfusion period, the ATP pool had recovered to an appreciable extent (3.01 +/- 0.11, n = 9) and was higher when 1.0 mM inosine had been infused (3.44 +/- 0.11, n = 7). Thus, inosine increased coronary flow dose dependently and, as a consequence, the function of the isolated perfused working heart both under control conditions and during the postischemic reperfusion period.

Adenine Nucleotides↗